Self-sealing apparatus for chemical reaction vessel

ABSTRACT

According to an aspect of the invention, an apparatus for self-sealing of a reaction vessel, such that the reaction vessel may be repeatedly accessed by a fluid transfer mechanism and subsequently self-sealed, is detailed. The reaction vessel has an access opening, and the apparatus comprises a cap, a ball which is comprised of a magnetizable material (such as a ferrous metal), and a ring magnet. The cap is sized to fit over the reaction vessel access opening, and has an access port. The cap has an internal surface which faces the reaction vessel, and an external surface, which faces away from the reaction vessel. The ball is sized to fit over the cap access port, such that a portion of the ball seats partially in the cap access port on the cap internal surface, thus sealing the cap access port. According to an aspect of the invention, the ball may be comprised of a ferromagnetic material, or a magnetizable material that is preferably magnetized. The ring magnet produces a magnetic field, and is mounted to the cap on the cap external surface. The ring magnet is spaced from the cap such that the magnetic field is sufficient to hold the ball in the cap access port, and to reseat the ball in the cap access port after the reaction vessel is accessed.

This application is a divisional on U.S. patent application Ser. No.10/899,995, filed on Jul. 27, 2004 now abandoned.

BACKGROUND OF THE INVENTION

The present invention is in the field of chemical reaction vessels. Morespecifically this invention relates to sealing of reaction vessels whenadding or removing samples.

In general, addition of reagents to a reaction vessel is performedeither by injection with a syringe and cannula through a septum, or byopening a port mechanically and adding the material through the opening.Another method is to use non-septum piercing disposable pipette tipswhich are thrust through prescored septa. This method is used when highaccuracy and low cross contamination is desired, however, the essentialprescored septum suffers from poor sealing properties.

In the case of addition through the septum, many problems routinelyemerge. There are only a limited amount of times a septum can be piercedbefore it starts to leak at an unacceptable rate. Even one piercing maylead to a leak which could cause the loss of reagent and/orcontamination, and change the outcome of an experiment in anunacceptable way. In the event that the tainted experimental result isnot appreciated, false conclusions could be reached. One way the priorart has attempted to overcome this is by replacing the septum after usein a counterflow of inert gas. This is a time consuming and complexprocedure. Further, septa are commonly abraded by the piercing action,resulting in septa particulates contaminating the experiment. Also,where the reaction vessel is subjected to conditions which produce arelatively high pressure in the vessel, this pressure commonly needs tovent to achieve accurate reagent delivery, and the way the septacommonly seals around the puncturing needle does not allow for adequateventing. In these situations, special grooved needles may be used, toallow for venting when the needles pierce the septa. However, theseneedles are more expensive, and contaminates may get caught in thegrooves affecting the experiment.

Opening the port mechanically requires external actuation, which becomeschallenging, complicated, and expensive with larger arrays of vessels.This is further complicated because any delay in closing the port allowsreagents to potentially escape.

A sealing mechanism for reaction vessels is desired which would notdeteriorate over time and use, which would not contaminate the reagents,which could allow for venting of pressure when necessary, which isself-actuating and self-sealing, and which would be easily adapted tolarge arrays of reaction vessels, such as those used in combinatorialchemistry.

SUMMARY OF THE INVENTION

According to an aspect of the invention, an apparatus for self-sealingof a reaction vessel, such that the reaction vessel may be repeatedlyaccessed by a fluid transfer mechanism and subsequently self-sealed, isdetailed. The reaction vessel has an access opening, and the apparatuscomprises a cap, a ball wherein the ball is comprised of a magnetizablematerial or is preferably magnetized, and a ring magnet. The cap issized to fit over the reaction vessel access opening, and has an accessport. The cap has an internal surface which faces the reaction vessel,and an external surface, which faces away from the reaction vessel. Theball is sized to fit over the cap access port, such that a portion ofthe ball seats partially in the cap access port on the cap internalsurface, thus sealing the cap access port. According to an aspect of theinvention, the ball may be comprised of a ferromagnetic material or amagnetizable material and may be magnetized. The ring magnet produces amagnetic field, and is mounted to the cap on the cap external surface.The ring magnet is spaced from the cap such that the magnetic field issufficient to hold the ball in the cap access port, and to reseat theball in the cap access port after the reaction vessel is accessed.

The present invention more specifically discloses an apparatus forself-sealing of a reaction vessel having an access opening, such thatthe reaction vessel may be repeatedly accessed by a fluid transfermechanism, and subsequently self-sealed, comprising:

a cap sized to fit over the reaction vessel access opening, and havingan access port therein, wherein said cap has an internal surface whichfaces the reaction vessel, and an external surface, which faces awayfrom the reaction vessel;

a ball sized to fit over said cap access port, wherein the ball iscomprised of a magnetizable material, such that a portion of said ballseats partially in said cap access port on said cap internal surface,sealing said cap access port; and

a ring magnet which produces a magnetic field, wherein said ring magnetis mounted to said cap on said cap external surface, and spaced fromsaid cap such that the magnetic field is sufficient to hold said ball insaid cap access port, and to reseat said ball in said cap access portafter said reaction vessel is accessed.

The present invention further discloses a method for sealing of areaction vessel having an access opening, such that the vessel may berepeatedly accessed by a fluid transfer mechanism, and subsequentlyself-sealed, comprising:

sealing said access opening with a cap having an access port, whereinsaid cap has an internal surface which faces the reaction vessel, and anexternal surface, which faces away from the reaction vessel, whereinsaid cap internal surface is tapered from said access port outwardtoward the reaction vessel;

seating a dipolar magnetic ball in said access port, wherein said ballis sized to fit over said access port, such that a portion of said ballseats partially in said access port, sealing said access port;

mounting a ring magnet which produces a magnetic field to said capexternal surface wherein said ring magnet is spaced from said cap suchthat the magnetic field is sufficient to hold said dipolar magnetic ballin said access port, and to reseat said dipolar magnetic ball in saidaccess port after said reaction vessel is accessed.

The subject invention also reveals an apparatus for use in combinatorialchemistry for self-sealing of reaction vessels in an array such as amicro-titer plate, wherein the reaction vessels have an access opening,such that the reaction vessels may be repeatedly accessed by a fluidtransfer mechanism, and subsequently self-sealed, comprising:

a cap sized to fit over the reaction vessel access opening, and havingan access port therein, wherein said cap has an internal surface whichfaces the reaction vessel, and an external surface, which faces awayfrom the reaction vessel;

a ball sized to fit over said cap access port, wherein the ball iscomprised of a magnetizable material such that a portion of said ballseats partially in said cap access port on said cap internal surface,sealing said cap access port; and

a ring magnet which produces a magnetic field, wherein said ring magnetis mounted to said cap on said cap external surface, and spaced fromsaid cap such that the magnetic field is sufficient to hold said ball insaid cap access port, and to reseat said ball in said cap access portafter said reaction vessel is accessed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front view of a reaction vessel according to an aspect ofthe invention.

FIG. 2 is a cross-sectional view of a portion of a self sealingapparatus, according to an aspect of the invention.

FIG. 3 is an isometric view of a cap according to an aspect of theinvention.

FIG. 4 is a bottom view of a cap seating a ball according to an aspectof the invention.

FIG. 5 is a bottom view of a cap according to an aspect of theinvention.

FIG. 6 is an exploded view of a reaction vessel self-sealing apparatusaccording to an aspect of the invention.

FIG. 7 is an isometric view of a cap according to an aspect of theinvention.

FIG. 8 is a cross section from FIG. 7.

FIG. 9 is a side view of a reaction vessel self-sealing apparatusinstalled on a reaction vessel according to an aspect of the invention.

FIG. 10 is a cross section from FIG. 9.

FIG. 11 is a cross section from FIG. 9.

FIG. 12 is a top view of a cap according to an aspect of the invention

FIG. 13 is a cross section from FIG. 12.

FIG. 14 is an isometric view of a cap according to an aspect of theinvention

FIG. 15 is a cross section from FIG. 14.

FIG. 16 is an isometric view of part of an array of reaction vessels ina micro-titer type device.

FIG. 16A is a cross section of a self-sealing apparatus of one aspect ofthis invention mounted on the upper portion of a reaction vessel.

FIG. 17 is a side view of a self-sealing reaction vessel having a neckportion and a body with a cap therefore shown in an explodedorientation.

FIG. 17A is a cross section of the upper portion of the self-sealingreaction vessel illustrated in FIG. 17.

FIG. 18 is a prospective view an array of reaction vessels in amicro-titer device.

FIG. 18A is a cross section view of a self-sealing reaction vessel inthe micro-titer device as illustrated in FIG. 18.

FIG. 19 is a prospective view of an array of reaction vessels in amicro-titer device in accordance with one aspect of this invention.

FIG. 19A is a cross section view of a self-sealing reaction in themicro-titer device as illustrated in FIG. 19.

DETAILED DESCRIPTION

Various aspects of the invention are presented in FIGS. 1-14 which arenot drawn to scale and in which like components are numbered alike.Referring now to FIGS. 1-14, according to an aspect of the invention, anapparatus 5 for self-sealing of a reaction vessel 70, such that thereaction vessel 70 may be repeatedly accessed by a fluid transfermechanism 80 and subsequently self-sealed, is shown. The reaction vessel70 has an access opening 72, and the apparatus 5 comprises a cap 20, afastening mechanism 100, a ball 30, and a ring magnet 40. A preferredembodiment of this invention is illustrated in FIG. 18A wherein thereaction vessel 70 is a Wheaton 3 mL glass autosampler vial, wherein thevessel is capped with a stopper 21 wherein the stopper is a Wheaton 13mm snap-on stopper with a 3.5 mm center bore, wherein the ring magnet 40has an outer diameter of 0.5 inches, an inner diameter of 0.28 inchesand a thickness of 0.125 inches wherein the ring magnet is of grade N40,and is comprised of NdFeB, and wherein the ball 30 is a spherical magnethaving a diameter of 0.186 inches, wherein the spherical magnet is ofgrade N40 and wherein the spherical magnet is comprised on NdFeB.

The cap 20 is sized to fit over the reaction vessel access opening 72,and has an access port 22. The cap 20 has an internal surface 24 whichfaces the reaction vessel 70, and an external surface 26, which facesaway from the reaction vessel 70. The cap 20 may fit over the reactionvessel in a variety of ways. According to an aspect of the invention,the fastening mechanism 100 comprises a threaded portion 102 on the cap20, and a mating threaded portion 104 on the reaction vessel 10. Thusthe cap 20 may screw onto the reaction vessel 70. In a further aspect ofthe invention, the fastening mechanism 100 comprises a pressure fitbetween the cap 20 and the reaction vessel 10, such that the cap 20 maybe snapped on to the reaction vessel 10. These are just two examples offastening mechanisms, and in no way limits the invention to thesemethods, as any suitable method of fastening the cap 20 to the reactionvessel 70 is within the purview of this invention.

The ball 30 is sized to fit over the cap access port 22, such that aportion of the ball 30 seats partially in the cap access port 22 on thecap internal surface 24, thus sealing the cap access port 22. The ballis essentially spherical in shape. According to an aspect of theinvention, the ball 30 may be comprised of a ferromagnetic material, oranother magnetizable material and is preferably magnetized. The ballwill typically be comprised of a material that can be permanentlymagnetized. Some representative examples of materials that can be usedinclude metals and ceramics selected from aluminum-nickel-cobalt(alnicos), strontium-iron (ferrites, also known as ceramics),neodymium-iron-boron (neo magnets, sometimes referred to as “supermagnets”), and samarium-cobalt. (The samarium-cobalt andneodymium-iron-boron families are collectively known as the rareearths.)

The ring magnet 40 produces a magnetic field, and is mounted to the cap20 on the cap external surface 26. The ring magnet 40 is spaced from thecap 20 such that the magnetic field is sufficient to hold the ball 30 inthe cap access port 22, and to reseat the ball 30 in the cap access port22 after the reaction vessel 70 is accessed. This spacing can beaccomplished for example, by using a spacing washer 42, or by thethickness of the cap 25.

According to a further aspect of the invention, the self-sealingapparatus 5 further comprises a sealing gasket 50 such as an O-ring,mounted to the cap 20 at the cap access port 22. The sealing gasket 50is sized to ring the cap access port 22, such that the ball 30 will seatin the sealing gasket 50.

In a preferred embodiment of the invention, the sealing gasket 50 isflush with the cap internal surface 24 (see FIGS. 2 and 8). In a furtherpreferred embodiment, the sealing gasket 50 is comprised of anelastomeric material. In most cases, a sealing gasket 50 with chemicallyinert properties is desired, so as not to risk contamination of thereagents. For example, the sealing gasket 50 may be made of an elastomerwhich is coated with Telfon® polymer or made of a fluoronated elastomer,such as Tefzel® fluoronated elastomer. These are just examples which maybe desirable, and in no way are intended to limit the sealing gasket 50material, as any application suitable material may be used.

In order to further insure a good seal between the reaction vessel 70and the cap 20, according to an aspect of the invention a cap gasket 29is mounted to the cap internal surface 24 between the cap internalsurface 24 and the reaction vessel walls 14.

According to another aspect of the invention, the ball 30 is magnetized.In a preferred embodiment, the ball 30 is a dipolar magnet. This allowsfor a stronger force between the ring magnet 40 and the ball 30, andtherefore seats the ball 30 more securely in the sealing gasket 50.

To further improve the reseating of the ball 30 after the reactionvessel 70 is accessed, the cap internal surface 24 is conical in shapeaccording to an aspect of the invention. In this configuration, the capaccess port 22 is closest to the ring magnet 40, and as the cap internalsurface 24 extends away from the cap access port 22, it gets fartheraway from the ring magnet 40.

To insure that the ball 30 does not prevent access by the fluid transfermechanism 80, or cause damage or bending of the fluid transfermechanism, according to an aspect of the invention the dimensions of theball 30 relative to the dimensions of the reaction vessel walls and thecap access port 22 are controlled. The cap 20 is mounted to the reactionvessel walls 74, wherein there is a distance 75 between the center line110 of the access port 20 and the reaction vessel walls 74. The ball 30has a diameter 32 which is less than the distance 75 between the centerline 110 of the access port 20 and the reaction vessel walls 74. Tofurther insure that the ball 30 does not prevent access by the fluidtransfer mechanism, or cause damage or bending of the fluid transfermechanism, according to an aspect of the invention, the distance 75should be greater than the diameter of the ball 30 plus the radius ofthe fluid transfer mechanism 80.

Another method of insuring that the ball 30 does not prevent access bythe fluid transfer mechanism 80 is by using a reaction vessel which hasa neck portion 76 and a body portion 78 wherein the distance 75 in theneck portion may be smaller than the diameter of the ball 30, but in thebody portion 78 the distance 75 is greater than the ball diameter 32. Inthis configuration, the neck portion 76 is shorter than the reach of thefluid transfer mechanism 80. Thus the fluid transfer mechanism 80 maypush the ball 30 down through the neck portion 76 until it reaches thebody portion 78 where it rolls out of the way of the fluid transfermechanism 80. The neck portion 76 must be short enough such that themagnetic field is strong enough to return the ball 30 to its seatedposition from the body portion 78. An example of an appropriate shapedreaction vessel 70 is what is commonly called a serum vial. In apreferred embodiment of the invention, the ring magnet 40 is integral tothe cap 20 (see FIGS. 7 and 8).

These types of reaction vessels are often accessed by a machine, whichdoes not aim for a specific part of the access opening 72, but rather aspecific point in space where the access opening 72 is supposed to be.Therefore the accuracy is limited by human error in positioning thereaction vessels 70, and positioning of the fluid transfer mechanism 80,such as a cannula, in the machine. To allow for proper functioning withsome error in these areas, according to a further aspect of theinvention, the apparatus 5 further comprises a guiding mechanism 60mounted to the cap external surface 26 for guiding the fluid transfermechanism 80 into the access port 22 (see FIG. 9). In a preferredembodiment the guiding mechanism 60 is a funnel shape. This can be donewith an external funnel apparatus, or, where the ring magnet 40 isintegral to the cap 20, the guiding mechanism 60 could comprise the capexternal surface 26 being tapered at the access port 22 (see FIGS. 14and 15). This is especially useful when large arrays of reactionvessels, such as when they are arranged in a micro-titer format, arebeing accessed simultaneously, such as is commonly done in combinatorialchemistry (see FIG. 16). One typical micro-titer format is a 96 block,with rows 8×12.

The self-sealing apparatus may be used in a micro-titer format. In sucha format, the cap 20 may be on the reaction vessel 10 beforeinstallation into this format, or the cap 20 may be located in the topmicro-titer plate 90. According to this aspect of the invention, the cap20 is mounted to the reaction vessel 70 by the clamping of the topmicro-titer plate 90 onto the block of reaction vessels, and this actsas the fastening mechanism. The self-sealing apparatus of this inventioncan be used in conjunction with virtually any vessel for storing,mixing, and/or reacting chemical agents. Such chemical reaction vesselsare most suitable for storing, mixing and/or reacting liquid chemicalagents and solid chemical agents that are dissolved or otherwisedispersed in a liquid. However, the chemical reaction vessel canoptionally be used in conjunction with chemicals that are in the solidor gas phase. For instance, reaction vessels that are equipped with theself-sealing apparatus of this invention are particularly useful incases where a liquid medium is sparged with a gas.

To further isolate the reactants in the reaction vessel 70, according toan aspect of the invention, the self-sealing apparatus 5 furthercomprises a septum 28 mounted to the cap external surface 26 (see FIGS.12 and 13). This is useful where it is important that no gas escape thereaction vessel 70. Combining the septum with the self-sealing apparatusinsures a positive seal even after piercing the septum, whereas theseptum alone may leak after initial or repeated piercings adverselyaffecting the reaction.

According to a further aspect of the invention, the cap 20 may becomprised of an elastomeric material. This elastomeric material shouldbe chemically inert for best results. In a preferred embodiment, theelastomeric cap external surface is planar, and the elastomeric capinternal surface comprises a protrusion into the reaction vessel,wherein the protrusion makes a ring of contact with the reaction vesselwalls. This ring of contact helps improve the seal between the cap andthe reaction vessel. A standard serum vial septum may be used as the capportion in this embodiment. This standard septum will have to bemodified to have a cap access port. In this embodiment, one method ofmounting the ring magnet would be to mount the ring magnet to anexternal plate, such as a micro-titer plate 90. Thus when the reactionvessel is mounted in the micro-titer format with this micro-titer plate90, the ring magnet will be in proper spatial relation to the ball.

1. A method for sealing of a reaction vessel having an access opening,such that the vessel is repeatedly accessed by a fluid transfermechanism, and subsequently self-sealed, comprising: sealing said accessopening with a cap having an access port, wherein said cap has aninternal surface which faces the reaction vessel, and an externalsurface, which faces away from the reaction vessel, wherein said capinternal surface is tapered from said access port outward toward thereaction vessel; seating a dipolar magnetic ball in said access port,wherein said ball is sized to fit over said access port, such that aportion of said ball seats partially in said access port, sealing saidaccess port; mounting a ring magnet which produces a magnetic field tosaid cap external surface wherein said ring magnet is spaced from saidcap such that the magnetic field is sufficient to hold said dipolarmagnetic ball in said access port, and to reseat said dipolar magneticball in said access port after said reaction vessel is accessed;transferring a fluid into the reaction vessel wherein the fluid transfermechanism pushes the ball down into the reaction vessel until it rollsout of the way of the fluid transfer mechanism, and wherein the fluid istransferred into the reaction vessel while the fluid transfer mechanismis in the reaction vessel with the ball being pushed out of the way ofthe fluid transfer mechanism; and withdrawing the fluid transfermechanism from the reaction vessel and allowing the ball to reseat inthe access port seal of the reaction vessel.
 2. The method of claim 1further comprising a sealing gasket mounted to said cap at said accessport, wherein said sealing gasket is sized to ring said access port,such that said ball will seat in said sealing gasket.
 3. The method ofclaim 2 wherein said sealing gasket is flush with said cap internalsurface.
 4. The method of claim 2 wherein said sealing gasket iscomprised of an elastomeric material.
 5. The method of claim 1 whereinsaid cap internal surface is conical in shape wherein said cap accessport is closest to said ring magnet.
 6. The method of claim 1 whereinthe reaction vessel has walls, wherein the access port has a center linewherein said cap is mounted to the reaction vessel walls, wherein thereis a distance between said access port and the reaction vessel walls,and wherein said ball has a diameter which is less than the distancebetween the center line of said access port and the reaction vesselwalls.
 7. The method of claim 1 wherein said ring magnet is integral tosaid cap.
 8. The method of claim 1 further comprising a guidingmechanism mounted to said cap external surface for guiding said fluidtransfer mechanism into said access port.
 9. The method of claim 8wherein said guiding mechanism is a funnel shape.
 10. The method ofclaim 8 wherein said ring magnet is integral to said cap, and saidguiding mechanism comprises said cap external surface being tapered atsaid access port.
 11. The method of claim 1 further comprising a septummounted to said cap external surface.
 12. The method of claim 1 whereinsaid fastening mechanism comprises a threaded portion on said cap and amating threaded portion on the reaction vessel.
 13. The method of claim1 wherein said fastening mechanism comprises a pressure fit between saidcap and the reaction vessel, such that said cap may be snapped onto thereaction vessel.
 14. The method of claim 1 wherein said fasteningmechanism comprises clamping a plate over said cap, thus clamping saidcap onto the reaction vessel.
 15. The method of claim 1 wherein saidball is magnetized.
 16. The method of claim 15 wherein said ball is adipolar magnet.
 17. The method of claim 1 wherein the reaction vessel isin an array on a micro-titer plate.
 18. The method of claim 1 whereinthe access opening is at the top of the reaction vessel.
 19. The methodof claim 1 which further comprises sparging the fluid transferred intothe reaction vessel with a gas.
 20. The method of claim 11 wherein theseptum is pierced by the fluid transfer mechanism when the fluid isbeing transferred into the reaction vessel.